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The protease inhibitor cystatin C is differentially expressed among dendritic cell populations, but does not control antigen presentation

El-Sukkari, D; Wilson, NS; Håkansson, Katarina LU ; Steptoe, RJ; Grubb, Anders LU ; Shortman, K and Villadangos, JA (2003) In Journal of Immunology 171(10). p.5003-5011
Abstract
Dendritic cells (DC) undergo complex developmental changes during maturation. The MHC class H (MHC H) molecules of immature DC accumulate in intracellular compartments, but are expressed at high levels on the plasma membrane upon DC maturation. It has been proposed that the cysteine protease inhibitor cystatin C (CyC) plays a pivotal role in the control of this process by regulating the activity of cathepsin S, a protease involved in removal of the MHC H chaperone E, and hence in the formation of MHC H-peptide complexes. We show that CyC is differentially expressed by mouse DC populations. CD8(+) DC, but not CD4(+) or CD4(-)CD8(-) DC, synthesize CyC, which accumulates in MHC II(+)Lamp(+) compartments. However, II processing and MHC H... (More)
Dendritic cells (DC) undergo complex developmental changes during maturation. The MHC class H (MHC H) molecules of immature DC accumulate in intracellular compartments, but are expressed at high levels on the plasma membrane upon DC maturation. It has been proposed that the cysteine protease inhibitor cystatin C (CyC) plays a pivotal role in the control of this process by regulating the activity of cathepsin S, a protease involved in removal of the MHC H chaperone E, and hence in the formation of MHC H-peptide complexes. We show that CyC is differentially expressed by mouse DC populations. CD8(+) DC, but not CD4(+) or CD4(-)CD8(-) DC, synthesize CyC, which accumulates in MHC II(+)Lamp(+) compartments. However, II processing and MHC H peptide loading proceeded similarly in all three DC populations. We then analyzed MHC H localization and Ag presentation in CD8(+) DC, bone marrow-derived DC, and spleen-derived DC lines, from CyC-deficient mice. The absence of CyC did not affect the expression, the subcellular distribution, or the formation of peptide-loaded MHC II complexes in any of these DC types, nor the efficiency of presentation of exogenous Ags. Therefore, CyC is neither necessary nor sufficient to control MHC II expression and Ag presentation in DC. Our results also show that CyC expression can differ markedly between closely related cell types, suggesting the existence of hitherto unrecognized mechanisms of control of CyC expression. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
171
issue
10
pages
5003 - 5011
publisher
American Association of Immunologists
external identifiers
  • pmid:14607896
  • wos:000186643300010
  • scopus:0242495719
ISSN
1550-6606
language
English
LU publication?
yes
id
08a4bd75-d02d-43e6-968e-1468b64fbbaf (old id 294973)
alternative location
http://www.jimmunol.org/cgi/content/abstract/171/10/5003
date added to LUP
2007-08-29 14:58:27
date last changed
2018-02-18 04:19:05
@article{08a4bd75-d02d-43e6-968e-1468b64fbbaf,
  abstract     = {Dendritic cells (DC) undergo complex developmental changes during maturation. The MHC class H (MHC H) molecules of immature DC accumulate in intracellular compartments, but are expressed at high levels on the plasma membrane upon DC maturation. It has been proposed that the cysteine protease inhibitor cystatin C (CyC) plays a pivotal role in the control of this process by regulating the activity of cathepsin S, a protease involved in removal of the MHC H chaperone E, and hence in the formation of MHC H-peptide complexes. We show that CyC is differentially expressed by mouse DC populations. CD8(+) DC, but not CD4(+) or CD4(-)CD8(-) DC, synthesize CyC, which accumulates in MHC II(+)Lamp(+) compartments. However, II processing and MHC H peptide loading proceeded similarly in all three DC populations. We then analyzed MHC H localization and Ag presentation in CD8(+) DC, bone marrow-derived DC, and spleen-derived DC lines, from CyC-deficient mice. The absence of CyC did not affect the expression, the subcellular distribution, or the formation of peptide-loaded MHC II complexes in any of these DC types, nor the efficiency of presentation of exogenous Ags. Therefore, CyC is neither necessary nor sufficient to control MHC II expression and Ag presentation in DC. Our results also show that CyC expression can differ markedly between closely related cell types, suggesting the existence of hitherto unrecognized mechanisms of control of CyC expression.},
  author       = {El-Sukkari, D and Wilson, NS and Håkansson, Katarina and Steptoe, RJ and Grubb, Anders and Shortman, K and Villadangos, JA},
  issn         = {1550-6606},
  language     = {eng},
  number       = {10},
  pages        = {5003--5011},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {The protease inhibitor cystatin C is differentially expressed among dendritic cell populations, but does not control antigen presentation},
  volume       = {171},
  year         = {2003},
}